THE HUMAN PRION DISEASE : KURU

1. THE LAUGHING DEATH: KURU
HIMACHAL INSTITUTE OF PHARMACY
PRESENTED BY : KRITIKA SAINI
B.PHARMACY 4TH YEAR
ROLL NO: 17BPD1226
SUPERVISED BY : DR.RAMANDEEP SINGH
(HOD) PhD. PHARMACOLOGY

2. The laughing death : KURU
https://youtu.be/ZHOy6hiUcyA[1]
FIG.1[2].

3. CONTENTS
 AIM AND OBJECTIVE
 INTRODUCTION
 REVIEW OF LITERATURE
 REFERENCES
Fig.2[3].

4. AIM
 TO REVIEW HUMAN PRION DISEASE.
OBJECTIVES
• AN OVERVIEW OF PRIONS AND DISEASES CAUSED BY
PRIONS.
• TO STUDY THE PRION EPIDEMIC IN EARLY 1900’s.

5. KURU
 A rare and fatal brain disorder.
 It was discovered in the early 1900’s , by 1950’s, Kuru
was rampant among the South Fore tribe [4].
 Ritualistic cannibalism.
 Majority of deaths- women ,children and elderly.
Incubation period > 30 days to several years[5].
 Only witnessed in the highlands of Papua New Guinea
among the Fore, a tribe of remote people.
 It is a prion disease.
 Individuals with kuru had infectious brain tissue due to
consumption of their deceased relatives.
Introduction

6. Causative Agent - THE PRIONS
 Smaller than smallest known virus.
 Kuru is caused by prions, these are the proteinaceous
infectious particles causing degenerative brain disease.
 Prions are single molecules containing 250 amino acids
and MW is 36kDa [6].
 They are abnormal variants of normal proteins, usually
misfolded proteins.(PrPC to PrPSc)They lack nucleic acid.
 They have the ability to convert the normal forms that they
come into contact with abnormal form.

7. Prion disease in humans and animals
 KURU.
 CJD( creutzfeldt- jacob
disease).
 Fatal familial insomnia.
 Scrapie in sheep and goat
(animals).
 German-straussler scheinker
syndrome.
 Bovine spongiform
encephalopathy(BSE).
 Mad cow disease.[7]

8. What is PrPc and PrPSc ?
NORMAL PROTEIN
• PrPc
• Secondary structure dominated
by alpha helices.
• Easily soluble.
• Easily digested by proteases.
• Encoded by PRNP gene in
humans.
ABNORMAL PROTEIN
• PrPSc
• Secondary structure is dominated by
beta conformation.
• When PrPSc contacts PrPc it
converts it into abnormal form.
• Insoluble in all conditions.
• Extremely resistant to digestion by
proteases.

9. Symptoms
 Early symptoms include general unsteadiness,
deterioration and slurring of speech, tremor and shivering.
 The word “kuru” in Fore means to shiver[8].
The following 3 phases are:
 Initial phase - ataxia, dysarthria and tremor.
 Sedentary - worsening of tremor and mood instability.
 Terminal - progression of dysarthria and dysphagia.
 Other includes outbursts of laughter, shock like muscles
jerks, depression [9].

10. Diagnosis
• Tonsil biopsy,
• Post mortem definitive diagnosis,
• Histopathological examination of biopsied or autopsied brain,
• ECG, KFT, LFT.[10-12]
• Dominant clinical features are fatigue, insomnia, depression, weight loss, pain
sensations and headaches.
PRION
AFFECTED
BRAIN

11. • Alpers .P. Michael (2008);
Kuru is a fatal transmissible spongiform encephalopathy. When first investigated in
1957 it was found to be present in epidemic proportions, with approximately 1000
deaths in the first 5 years, 1957–1961. Monitoring the progress of the epidemic
carried out by epidemiological surveillance in the field for 50 years. From its peak,
the number of deaths from kuru declined to 2 in the last 5 years, indicating that the
epidemic is approaching its end. The mode of transmission of the prion agent of kuru
was the local mortuary practice of transmutation. The prohibition of this practice in
the 1950s led to the decline of epidemic[13].
• Lindenbaum S. (2008);
To understand kuru and solve the problems of its cause and transmission required
the integration of knowledge from both anthropological and medical research.
Anthropological studies elucidated the origin and spread of kuru, the local mortuary
practices of endocannibalism, the social effects of kuru, the life of women and child-
rearing practices, the kinship system of the Fore and their willingness to incorporate
outsiders into it, the myths, folklore and history of the Fore and their neighbors,
sorcery as a powerful social phenomenon and way of explaining the causation of
disease, and concepts of the treatment of disease [14].
Review Of Literature

12. • Sakudo Akikazu (2011);
Prion is an infectious particle composed of an abnormal isoform of the prion
protein (PrPSc) and causes prion diseases such as bovine spongiform
encephalopathy (BSE), Creutzfeldt-Jakob disease (CJD) and scrapie. (PrPC), which
plays roles in normal functions such as anti-oxidative stress. PrPSc is derived from
PrPC and produced by conformational conversion. Prion is notorious as a resistant
pathogen, being difficult to inactivate with conventional sterilization procedures.
To prevent prion disease the use of alcohol treatment, autoclave (121 ̊C, 20 min)
and γ-ray irradiation, which are used for disinfection, antisepsis or sterilization of
viruses and bacteria, are not effective against prion[15].
• Liberski. P. Pawel et al.,(2012);
Kuru was the first human transmissible spongiform encephalopathy (TSE) or prion
disease identified, occurring in the Fore linguistic group of Papua New Guinea. A
fatal cerebellar ataxic syndrome, usually followed by choreiform and athetoid
movements. Kuru imposed a strong balancing selection on the Fore population,
with individuals homozygous for the 129 Met allele of the gene (PRNP) encoding
for prion protein (PrP) being the most susceptible. The decline in the incidence of
kuru in the Fore has been attributed to the exhaustion of the susceptible genotype
and ultimately by discontinuation of exposure via cannibalism[16].

13. • Ironside Jw et al., (2017);
The human prion diseases comprise Creutzfeldt-Jakob disease, variably protease-
sensitive prionopathy, Gerstmann-Sträussler-Scheinker disease, fatal familial
insomnia, and kuru. Each is a uniformly fatal rare neurodegenerative disease in
which conformational changes in the prion protein are thought to be the central
pathophysiologic event. The intensive study of these diseases continues to inform
on neurodegenerative mechanisms and the role of protein misfolding in more
common neurodegenerative diseases such as Parkinson disease and Alzheimer
disease [17].
• Agata Gajos et al.,(2019);
Kuru, the first human prion disease was transmitted to chimpanzees by D.
Carleton Gajdusek (1923–2008). Here we summarize the history of this seminal
discovery, its anthropological background, epidemiology, clinical picture,
neuropathology, and molecular genetics. We provide descriptions of electron
microscopy and confocal microscopy of kuru amyloid plaques retrieved from a
paraffin-embedded block of an old kuru case, named Kupenota. The discovery of
kuru opened new vistas of human medicine and was pivotal in the subsequent
transmission of Creutzfeldt–Jacob disease, as well as that of bovine spongiform
encephalopathy(BSE) had for transmission to humans[18].

14. Curing the incurable - TREATMENT
• There are no treatments that could control or cure Kuru or any other TSE
disease. Rather than, discouraging the practice of cannibalism could stop
this epidemic.
• Many experimental drugs are under investigation like Quinacrine, congo
red reagent, phenothiazines, pentosan polysulphate.[11]
• A homeopathic treatment that could gave little relief in past was swaying
fronds of the casuarina tree.[12]
• Symptomatic treatment, supportive care to be taken to get relief from the
disease.

15. methodology
In this study, bibliographic investigation was carried out during Feb. 2021, by
analyzing classical textbooks and peer reviewed papers, consulting worldwide
accepted scientific databases INFLIBNET, NISCAR, SCOPUS, SCIELO,
MEDLINE, PUBMED and Google scholar.
Only relevant studies published in English were considered. Further, detailed
information on review status of KURU: The Laughing Death, has been discussed.

16. REFERENCES
1. https://youtu.be/ZHOy6hiUcyA
2. https://sublevelsounds.com/album/transmissible-spongiform-encephalopathy-kuru-double-
vinyl-2013
3. https://norkinvirology.files.wordpress.com/2015/04/kuru.jpg
4. https://www.coursehero.com/file/27812143/KURUppt/ rampant
5. www.cfsph.iastate.edu> TSEPPT
6. www.ncbi.nlm.nih.gov
7. https://www.cdc.gov/prions/index.html
8. https://www.ninds.nih.gov/Disorders/All-Disorders/Kuru-Information-Page
9. Lindenbaum Shirley, Sikorska Beata. A review article on: KURU: Genes, Cannibals and
Neuropathology. Journal of Neuropathol Exp Neurol, Vol.71, No.2 ,Feb 2012, page.no.92.
10. http://www.authorstream.com/Presentation/aSGuest135838-1426977-prion/
11. http://www.authorstream.com/Presentation/aSGuest135838-1426977-prion/
12. Gajos Agata, Sikorska Beata Liberski P. Paweł. A Review on Kuru, the First Human Prion
Disease. www.mdpi.com/journal/viruses, Viruses 2019, 11, 232; doi:10.3390/v11030232,
page.no. 4 of 25
13. Alpers P. Michael. A review on the epidemiology of Kuru: monitoring the epidemic from its
peak to its end. Philosophical Transactions Of The Royal Society,2008. (The Royal Society
Journal), 363, page.no. 3707.
14. Shirley Lindenbaum. Understanding kuru: the contribution of anthropology and medicine.
Philos Trans R Soc Lond B Biol Sci. 2008; 363: 3715-3720. Ref.: https://goo.gl/LjygFe.
15. Sakudo Akikazu, Ano Yasuhisa, Nitta Kayako, Ikuta Kazuyoshi. A review on; Fundamentals of
prions and their inactivation. International Journal Of Molecular Medicine, vol 27, page.no.
483, 2011.

17. 16. Liberski.P.Pawel, Lindenbaum Shirley, Sikorska Beata. A review article on: KURU: Genes, Cannibals
and Neuropathology. Journal of Neuropathol Exp Neurol, Vol.71, No.2 ,Feb 2012, page.no.92.
17. Ironside JW, Ritchie DL, Head MW2. Prion diseases. Handb Clin Neurol. 2017; 145: 393-403.
18. Gajos Agata, Sikorska Beata Liberski P. Paweł. A Review on Kuru, the First Human Prion Disease.
www.mdpi.com/journal/viruses, Viruses 2019, 11, 232; doi:10.3390/v11030232, page.no. 1 of 25.
SMARTCANNIBALSDON’T EATBRAINS!!!